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However, the effects of LXRs on the capillarization of liver sinusoidal endothelial cells (LSECs) in liver fibrosis remain undetermined. Here, we demonstrated that LXR\u03b1 plays an important role in LSECs capillarization in a manner that involved Hedgehog (Hh) signaling. We found that LXR\u03b1 expression in LSECs was increased in the carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)-induced fibrosis model. LXR\u03b1 deletion markedly exacerbated CCl<jats:sub>4<\/jats:sub>-induced lesions assessed by histopathology, as well as inflammation and collagen deposition. Furthermore, capillarization of the sinusoids was aggravated in CCl<jats:sub>4<\/jats:sub> -treated LXR\u03b1-deficient mice, as evidenced by increased CD34 expression, the formation of continuous basement membranes and aggravation of the loss of fenestrae. <jats:italic>In vitro<\/jats:italic>, LXR agonist could maintain freshly isolated LSECs differentiation on day 3. Furthermore, LXR\u03b1 deletion led to increased expression of Hedgehog (Hh)-regulated gene in LSECs in the injured liver. Conversely, the LXR agonist could inhibit the Hh pathway in cultured LSECs. These responses indicated that LXR\u03b1 suppressed the process of LSECs capillarization by repressing Hh signaling. Overall, our findings suggest that LXR\u03b1, by restoring the differentiation of LSECs, may be critical for the regression of liver fibrosis.<\/jats:p>","DOI":"10.1038\/srep21309","type":"journal-article","created":{"date-parts":[[2016,2,18]],"date-time":"2016-02-18T12:05:19Z","timestamp":1455797119000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Liver X receptor \u03b1 is essential for the capillarization of liver sinusoidal endothelial cells in liver injury"],"prefix":"10.1038","volume":"6","author":[{"given":"Yan","family":"Xing","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuzhang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,2,18]]},"reference":[{"key":"BFsrep21309_CR1","doi-asserted-by":"publisher","first-page":"S54","DOI":"10.1002\/hep.21060","volume":"43","author":"V Racanelli","year":"2006","unstructured":"Racanelli, V. & Rehermann, B. 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